Cyclopropylamine → 1-cyclopropyl-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea

Participants

Reaction Steps

A solution of 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline (51 mg, 0.15 mmol) in dichloromethane (4 mL) was treated with triphosgene (23 mg, 0.08 mmol) as a solution in dichloromethane (1 mL). After the passage of 5 minutes, the appropriate nucleophile—in the case, cyclopropylamine (104 μL, 10 equivalents, 1.5 mmol)—was added to the 3-(6-(4-isocyanatophenyl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (“isocyanate”) mixture. The reaction mixture was concentrated to dryness under reduced pressure. The residue was purified by reverse-phase high performance liquid chromatography using a Phenomenex Prodigy 21 mm×250 mm column, running a gradient elution of 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 90% acetonitrile to provide 1-cyclopropyl-3-{4-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenyl}urea. MS (ES+): 420.2 (M+H)+

Provenance & Evidence